This proposal examines the hypothesis that right sided events affecting venous return, particularly the development of vascular waterfalls, are the major determinants of respiration's influence on the cardiovascular system during spontaneous and positive pressure ventilation. The specific aims seek to systematically develop a critical body of knowledge to explain how ventilatory produced stresses affect venous return under normal and pathologic states by combining a new method for measuring blood flow in veins with measures of vascular and surface pressures in the thorax and abdomen in intact and isolated liver preparations in the dog and pig. Computer modelling will be used to test hypotheses prospectively against experimental results. The dominant role of abdominal rather than thoracic pressures in determining venous return moves the focus of respiration's influence from the thorax to the abdomen. By developing the concept of abdominal vascular zone conditions (AVZC) similar to those describes in the lung, much of the confusion in the literature on the effects of changes in thoracic or abdominal pressures on cardiac output can be resolved. The concept of AVZC, locally within organs, regionally within the abdomen, and generally at the boundaries of the abdominal compartment is the unifying theme of this proposal. The same stress may produce an increase in venous return in one AVZC, but a decrease in another AVZC. Ventilatory stresses placed on the abdominal vascular compartments could contribute to circulatory and hepatic failure with ventricular dysfunction or sepsis to be modelled by endotoxin infusion. Understanding how ventilatory stresses produce substantial changes in venous return is directly related to understanding venous return from the same beds during CPR when externally applied stresses to the thorax and abdomen will alter the AVZC. Testing the usefulness of the AVZC to account for total and regional venous return over a wide spectrum of clinically relevant states should provide valuable information to physiologists and clinicians.